Combined lysis protocol for comprehensive cell lysis

Disclosed are methods for lysis of cells, such as bacteria present in microbiomes, that combine three lysis steps—(1) heat, (2) detergent and (3) base—into a single step and that can be completed in a short period of time, e.g., a few minutes. The methods combine a normally incompatible detergent and base lysis, allows for simplified removal of detergent after lysis, and importantly, yields improved quantities of genomic DNA (gDNA) from difficult to lyse bacteria.